Electrochemical CO2 reduction reaction on cost-effective oxide-derived copper and transition metal–nitrogen–carbon catalysts

The electrochemical CO₂ reduction reaction (CO₂RR) either to generate multicarbon (C₂₊) or single carbon (C₁) value-added products provides an effective and promising approach to mitigate the high CO₂ concentration in the atmosphere and promote energy storage. However, cost-effectiveness of catalytic materials limits practical application of this technology in the short term. Herein, we summarize and discuss recent and advanced works on cost-effective oxide-derived copper catalysts for the generation of C₂₊ products (hydrocarbons and alcohols) and transition metal–nitrogen–doped carbon electrocatalytic materials for C₁ compounds production from CO₂RR. We think they represent suitable electrocatalyst candidates for scaling up electrochemical CO₂ conversion. This short review may provide inspiration for the future design and development of innovative active, cost-effective, selective and stable electrocatalysts with improved properties for either the production of C₂₊ (alcohols, hydrocarbons) or carbon monoxide from CO₂RR.     

Nanoarchitectonics beyond Self‐Assembly: Challenges to Create Bio‐Like Hierarchic Organization

Incorporation of non‐equilibrium actions in the sequence of self‐assembly processes would be an effective means to establish bio‐like high functionality hierarchical assemblies. As a novel methodology beyond self‐assembly, nanoarchitectonics, which has as its aim the fabrication of functional materials systems from nanoscopic units through the methodological fusion of nanotechnology with other scientific disciplines including organic synthesis, supramolecular chemistry, microfabrication, and bio‐process, has been applied to this strategy. The application of non‐equilibrium factors to conventional self‐assembly processes is discussed on the basis of examples of directed assembly, Langmuir–Blodgett assembly, and layer‐by‐layer assembly. In particular, examples of the fabrication of hierarchical functional structures using bio‐active components such as proteins or by the combination of bio‐components and two‐dimensional nanomaterials, are described. Methodologies described in this review article highlight possible approaches using the nanoarchitectonics concept beyond self‐assembly for creation of bio‐like higher functionalities and hierarchical structural organization.     

Photon Equivalents as a Parameter for Scaling Photoredox Reactions in Flow: Translation of Photocatalytic C−N Cross‐Coupling from Lab Scale to Multikilogram Scale

With the development of new photocatalytic methods over recent decades, the translation of these chemical reactions to industrial‐production scales using continuous‐flow reactors has become a topic of increasing interest. In this context, we describe our studies toward elucidating an empirically derived parameter for scaling photocatalytic reactions in flow. By evaluating the performance of a photocatalytic C?N cross‐coupling reaction across multiple reactor sizes and geometries, it was demonstrated that expressing product yield as a function of the absorbed photon equivalents provides a predictive, empirical scaling parameter. Through the use of this scaling factor and characterization of the photonic flux within each reactor, the cross‐coupling was scaled successfully from the milligram scale in batch to a multi‐kilogram reaction in flow.     

Cell Engineering with Functional Poly(oxanorbornene) Block Copolymers

Cell‐based therapies are gaining prominence in treating a wide variety of diseases and using synthetic polymers to manipulate these cells provides an opportunity to impart function that could not be achieved using solely genetic means. Herein, we describe the utility of functional block copolymers synthesized by ring‐opening metathesis polymerization (ROMP) that can insert directly into the cell membrane via the incorporation of long alkyl chains into a short polymer block leading to non‐covalent, hydrophobic interactions with the lipid bilayer. Furthermore, we demonstrate that these polymers can be imbued with advanced functionalities. A photosensitizer was incorporated into these polymers to enable spatially controlled cell death by the localized generation of ¹O₂ at the cell surface in response to red‐light irradiation. In a broader context, we believe our polymer insertion strategy could be used as a general methodology to impart functionality onto cell‐surfaces.     

BIMP‐Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones

A bifunctional iminophosphorane (BIMP)‐catalysed enantioselective synthesis of α,β‐unsaturated cyclohexenones through a facially selective 1,3‐prototropic shift of β,γ‐unsaturated prochiral isomers, under mild reaction conditions and in short reaction times, on a range of structurally diverse substrates, is reported. α,β‐Unsaturated cyclohexenone products primed for downstream derivatisation were obtained in high yields (up to 99 %) and consistently high enantioselectivity (up to 99 % ee). Computational studies into the reaction mechanism and origins of enantioselectivity, including multivariate linear regression of TS energy, were carried out and the obtained data were found to be in good agreement with experimental findings.     

Emission Control by Molecular Manipulation of Double‐Paddled Binuclear PtII Complexes at the Air‐Water Interface

Molecular functions depend on conformations and motions of the corresponding molecular species. An air–water interface is a suitable asymmetric field for the control of molecular conformations and motions under a small applied force. In this work, double‐paddled binuclear Pt^II complexes containing pyrazole rings linked by alkyl spacers were synthesized and their orientations and emission properties dynamically manipulated at the air–water interface. The complexes emerge from water with concurrent variation of interface orientation of the planes of the Pt^II complexes from perpendicular to parallel during mechanical compression suggesting a unique ‘submarine emission‘. Phosphorescence of the complexes is quenched at the air–water interface prior to monolayer formation with intensities subsequently rapidly increasing during monolayer compression. These results indicate that asymmetric reactions and motions might be controlled by applying mechanical force at the air–water interface.     

How well does molecular simulation reproduce environment-specific conformations of the intrinsically disordered peptides PLP,TP2 and ONEG?

Understanding the conformational ensembles of intrinsically disordered proteins and peptides (IDPs) in their various biological environments is essential for understanding their mechanisms and functional roles in the proteome, leading to a greater knowledge of, and potential treatments for, a broad range of diseases. To determine whether molecular simulation is able to generate accurate conformational ensembles of IDPs, we explore the structural landscape of the PLP peptide (an intrinsically disordered region of the proteolipid membrane protein) in aqueous and membrane-mimicking solvents, using replica exchange with solute scaling (REST2), and examine the ability of four force fields (ff14SB, ff14IDPSFF, CHARMM36 and CHARMM36m) to reproduce literature circular dichroism (CD) data. Results from variable temperature (VT) ¹H and Rotating frame Overhauser Effect SpectroscopY (ROESY) nuclear magnetic resonance (NMR) experiments are also presented and are consistent with the structural observations obtained from the simulations and CD. We also apply the optimum simulation protocol to TP2 and ONEG (a cell-penetrating peptide (CPP) and a negative control peptide, respectively) to gain insight into the structural differences that may account for the observed difference in their membrane-penetrating abilities. Of the tested force fields, we find that CHARMM36 and CHARMM36m are best suited to the study of IDPs, and accurately predict a disordered to helical conformational transition of the PLP peptide accompanying the change from aqueous to membrane-mimicking solvents. We also identify an α-helical structure of TP2 in the membrane-mimicking solvents and provide a discussion of the mechanistic implications of this observation with reference to the previous literature on the peptide. From these results, we recommend the use of CHARMM36m with the REST2 protocol for the study of environment-specific IDP conformations. We believe that the simulation protocol will allow the study of a broad range of IDPs that undergo conformational transitions in different biological environments.

A protocol for simulating intrinsically disordered peptides in aqueous and hydrophobic solvents is proposed. Results from four force fields are compared with experiment. CHARMM36m performs the best for the simulated IDPs in all environments.     

Stealth Luminescent Organic Nanoparticles Made from Quadrupolar Dyes for Two-Photon Bioimaging: Effect of End-Groups and Core

Molecular-based Fluorescent Organic Nanoparticles (FONs) are versatile light-emitting nano-tools whose properties can be rationally addressed by bottom-up molecular engineering. A challenging property to gain control over is the interaction of the FONs’ surface with biological systems. Indeed, most types of nanoparticles tend to interact with biological membranes. To address this limitation, we recently reported on two-photon (2P) absorbing, red to near infrared (NIR) emitting quadrupolar extended dyes built from a benzothiadiazole core and diphenylamino endgroups that yield spontaneously stealth FONs. In this paper, we expand our understanding of the structure-property relationship between the dye structure and the FONs 2P absorption response, fluorescence and stealthiness by characterizing a dye-related series of FONs. We observe that increasing the strength of the donor end-groups or of the core acceptor in the quadrupolar (D-π-A-π-D) dye structure allows for the tuning of optical properties, notably red-shifting both the emission (from red to NIR) and 2P absorption spectra while inducing a decrease in their fluorescence quantum yield. Thanks to their strong 1P and 2P absorption, all FONs whose median size varies between 11 and 28 nm exhibit giant 1P (10⁶ M⁻¹.cm⁻¹) and 2P (10⁴ GM) brightness values. Interestingly, all FONs were found to be non-toxic, exhibit stealth behaviour, and show vanishing non-specific interactions with cell membranes. We postulate that the strong hydrophobic character and the rigidity of the FONs building blocks are crucial to controlling the stealth nano-bio interface.     

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent K_D of 50 nm  and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.     

Coinage Metal Complexes of Bis(quinoline-2-ylmethyl)phenylphosphine-Simple Reactions Can Lead to Unprecedented Results

The different coordination behavior of the flexible yet sterically demanding, hemilabile P,N ligand bis(quinoline-2-ylmethyl)phenylphosphine ( bqmpp ) towards selected Cu^I, Ag^I and Au^I species is described. The resulting X-ray crystal structures reveal interesting coordination geometries. With [Cu(MeCN)₄]BF₄, compound 1 [Cu₂(bqmpp)₂](BF₄)₂ is obtained, wherein the copper(I) atoms display a distorted square planar and square pyramidal geometry. The steric demand and π-stacking of the ligand allow for a short Cu⋅⋅⋅Cu distance (2.588(9) Å). Cu^I complex 2 [Cu₄Cl₃(bqmpp)₂]BF₄ contains a rarely observed Cu₄Cl₃ cluster, probably enabled by dichloromethane as the chloride source. In the cluster, even shorter Cu⋅⋅⋅Cu distances (2.447(1) Å) are present. The reaction of Ag[SbF₆] with the ligand leads to a dinuclear compound ( 3 ) in solution as confirmed by ³¹P{¹H} NMR spectroscopy. During crystallization, instead of the expected phosphine complex 3 , a tris(quinoline-2-ylmethyl)bisphenyl-phosphine ( tqmbp ) compound [Ag₂(tqmbp)₂](SbF₆)₂ 4 is formed by elimination of quinaldine. The Au(I) compound [Au₂(bqmpp)₂]PF₆ ( 5 ) is prepared as expected and shows a linear arrangement of two phosphine ligands around Au^I.